Polycation-based DNA complexes for tumor-targeted gene deliveryin vivo

Abstract

Background Efficient and target‐specific in vivo gene delivery is a major challenge in gene therapy. Compared to cell culture application, in vivo gene delivery faces a variety of additional obstacles such as anatomical size constraints, interactions with biological fluids and extracellular matrix, and binding to a broad variety of non‐target cell types. Methods Polycation‐based vectors, including adenovirus‐enhanced transferrinfection (AVET) and transferrin‐polyethylenimine (Tf‐PEI), were tested for gene delivery into subcutaneously growing tumors after local and systemic application. DNA biodistribution and reporter gene expression was measured in the major organs and in the tumor. Results Gene transfer after intratumoral application was 10–100 fold more efficient with Tf‐PEI/DNA or AVET complexes in comparison to naked DNA. Targeted gene delivery into subcutaneously growing tumors after systemic application was achieved using electroneutral AVET complexes and sterically stabilized PEGylated Tf‐PEI/DNA complexes, whereas application of positively charged polycation/DNA complexes resulted in predominant gene expression in the lungs and was associated by considerable toxicity. Conclusion For systemic application, the physical and colloidal parameters of the transfection complexes, such as particle size, stability, and surface charge, determine DNA biodistribution, toxicity, and transfection efficacy. By controlling these parameters, DNA biodistribution and gene expression can be targeted to different organs. Copyright © 1999 John Wiley & Sons, Ltd.

Systemic Delivery of DNA or siRNA Mediated by Linear Polyethylenimine (L-PEI) Does Not Induce an Inflammatory Response

“…Complexes were prepared in 5% glucose in order to generate stable complexes (of at least 24 h) whose size is adapted to in vivo experiments, i.e. around 100 nm in diameter [personal data and (33)]. The N/P ratio of 8 was used since it gives the highest transfection efficiency (data not shown).…”

Opposing Roles of Syndecan-1 and Syndecan-2 in Polyethyleneimine-mediated Gene Delivery

“…The linear and branched PEI (BPEI) 25-kDa forms have been shown to be among the most efficient non-viral vectors for in vitro (6 -8) and in vivo (7)(8)(9)(10)(11)(12) gene delivery. A key characteristic of PEIs resides in their intrinsic buffering capacity, a feature also known as the proton sponge effect (1).…”

Nanotechnology and its implications in therapeutics

“…In general, polyplexes reveal optimal transfection efficiency when they have a positive net charge generated by the presence of more a cationic polymer than DNA [51]. This allows the polyplexes to interact efficiently with the negatively charged cell surface proteoglycans that mediate subsequent endocytosis [52]. Erythrocyte aggregation and/or interaction with plasma components such as albumin and fibrinogen can occur upon the intravenous administration of positively charged polyplexes.…”